Although colorectal cancer is the second leading cause of cancer deaths for men and women in the United States, it would be largely preventable if its precursor lesions were detected and removed early. Most colorectal cancers develop from sessile or pedunculated polypoid neoplasms. Early removal of such neoplasms has been observed to reduce the occurrence of colorectal carcinoma. Computed tomographic colonography (CTC), or virtual colonoscopy, has become an alternative technique for providing mass screening for colorectal carcinoma due to recent large-scale, multi-center clinical trials, including the National CT Colonography Trial. However, for CTC to be truly deployed for the 70 million people eligible for screening in the U.S., it should be easy for the patients to tolerate, and should have high accuracy in detecting polyps. One of the difficulties with total colon examination, including CTC, is low patient adherence to the rigorous cathartic bowel cleansing that is used for bowel preparation prior to the examination. Laxative-free CTC (lfCTC) is an emerging technique for eliminating rigorous cathartic cleansing from the bowel preparation used in current CTC. Although promising, anticipated difficulties with lfCTC include a large amount of solid residual fecal material present in the colon, and variations in diagnostic performance among readers who interpret lfCTC images because of the distracting residual solid stool in detecting small polyps as well as flat lesions. For addressing these difficulties, the short-term goal in this project is to develop an lfCTC interpretation system that assists radiologists in detecting colorectal lesions (polyps and flat lesions) quickly and accurately. This proposal aims at developing two components in the lfCTC interpretation (1) A high-performance laxative-free computer-aided detection (lfCAD) scheme, which automatically and accurately detects polyps and flat lesions in lfCTC images; and (2) A laxative-free electronic cleansing (lfEC) scheme, which virtually cleanses the solid residual stool without prior physical bowel cleansing. Both schemes will be designed and optimized for lfCTC images. system: We hypothesize that the lfCTC interpretation (Aim 1) Establish lfCTC databases to develop and evaluate lfCAD and lfEC schemes; (Aim 2) Develop an lfCAD scheme for detection of colorectal lesions in lfCTC; (Aim 3) Develop an advanced lfEC scheme for artifact-free removal of the solid residual stool in lfCTC; (Aim 4) Evaluate the clinical benefit of an integrated lfCTC system will create diagnostic quality CTC images, yield clinically acceptable high detection performance of lesions, and improve radiologists' performance in the detection of colorectal lesions in lfCTC images. To explore these hypotheses, we propose the following specific aims: interpretation Successful development of the proposed lfCTC system. interpretation system will substantially advance the clinical implementation of image-based colon cancer screening in a large population, lead to an increased screening rate, promote the early diagnosis of colon cancer, and ultimately reduce the mortality due to colon cancer.